The present invention relates generally to the fields of microbiology, bacteriology and molecular biology. More specifically, the present invention relates to compositions and methods for preventing or treating infection in an animal caused by Burkholderia species.
Burkholderia mallei are non-motile bacterium responsible for glanders. This disease mainly affects horses, which are considered to be the natural reservoir for infection, although mules and donkeys are also susceptible (Neubauer et al. 2005 Journal of Veterinary Medicine Series B 52:201-5). Humans are accidental hosts of B. mallei following prolonged and close contact with infected animals. B. mallei infect humans by entering through open wounds and surfaces of the eyes or nose. Symptoms of glanders are dependent on the route of infection (Srinivasan et al. 2001 N Engl J Med 345:256-8). B. pseudomallei are motile bacteria causing melioidosis (Dance 1991 Clin Microbiol Rev 4:52-60). Melioidosis is a life-threatening disease that is mainly acquired through skin inoculation or pulmonary contamination, although other routes have been documented. This saprophyte inhabitant of soil environments is mainly encountered in Southeast Asia and northern Australia, but is sporadically isolated in subtropical and temperate countries (Stone 2007 Science 317:1022-24).
Both Burkholderia species are highly pathogenic and are classified as such in list B by the Centers for Disease Control and Prevention (Horn 2003 Surgical Infections. 4:281-87). Burkholderia infections are difficult to treat with antibiotics and there are several reports that indicate it is feasible to protect against melioidosis, at least in animal models of disease, with non-living vaccines (Nelson et al. 2004 J Med Microbiol 53:1177-82). There has also been some progress in identifying partially protective subunits. Passively administered antisera raised against flagellin, polysaccharide, or conjugates of polysaccharide and flagellin, protect diabetic rats against challenge with B. pseudomallei (Brett et al. 1994 Infect Immun. 62:1914-19; Brett and Woods 1996 Infect Immun. 64:2824-28; Bryan et al. 1994 Can J Infect Dis. 5:170-78). However, B. mallei are not motile and do not produce flagella. Moreover, the ability of flagellin to induce protection against an aerosol, or intranasal challenge has not been reported. Therefore, flagellin was assessed as a potential candidate for inclusion in a Burkholderia vaccine and found unsuitable. In contrast, all of the current evidence indicates that other surface-expressed or secreted proteins are immunogenic and structural similarity exists between the proteins in B. pseudomallei and B. mallei (Whitlock et al. 2007 FEMS Microbial. Lett. 277:115-22; Whitlock et al. 2008 Transactions of the Royal Society of Tropical Medicine & Hygiene 102 Suppl: S127-33).
The prior art is deficient in compositions and methods to protect animals (e.g., equine animals such as horses, donkeys, and mules as well as humans) against the Gram-negative bacterial pathogens Burkholderia mallei and B. pseudomallei by generating cross-protective immunity against both pathogens. The present invention fulfills this long-standing need and desire in the art.